Richards, Frederic M.

Frederic Middlebrook Richards (1925-2009  ) was an eminent protein structure and function researcher, and a member of the US National Academy of Sciences. He earned his B.S. at MIT in 1948, and his Ph.D. at Harvard in 1952. He joined the faculty at Yale in 1955, where he became Chair of the Biophysics Department in 1963 and subsequently, in 1967, presided over the merger of Biophysics and Biochemistry into the Department of Molecular Biophysics and Biochemistry, where he became the Sterling Professor. At Yale, he led the creation of one of the major structural research centers in the world. Seven of the ten faculty he hired are now Members of the National Academy of Sciences. His accomplishments include:


 * Discovered, in the late 1950's, that inactive fragments of an enzyme could be recombined and regain activity, presaging Anfinson's work in the 1960's (Nobel Prize 1972), leading to the paradigm that amino acid sequence specifies the native conformation required for function. Richards' work was done with pancreatic ribonuclease A. He found that it could be proteolytically cleaved into a peptide and a protein fragment which, when separated were inactive, but could regain activity when properly recombined. This work began while Richards was a postdoc with Kaj Linderstrøm-Lang (Carlsberg Lab, Copenhagen) and continued after he joined the faculty at Yale.
 * Solved the crystal structure of ribonuclease S in 1967 with faculty colleague Harold Wyckoff , including a structure with bound nucleoside monophosphate. This was the second enzyme structure solved, and the first protein crystallographic solution in the USA. See more about this structure below.
 * Demonstrated that RNAse S was enzymatically active in crystalline form, strongly supporting the conclusion that the conformations of proteins in crystals are relevant to their native conformations in solution.
 * Observed that the packing within a protein's core is as dense as organic molecules in molecular crystals such as sucrose . This followed from his development of computational methods for analysis of protein packing.
 * Developed, with B. K. Lee, computational methods for quantitating the solvent-accessible surfaces of proteins.
 * Developed the optical comparator (see photo at right) in 1968 while on sabbatical at Oxford University . Also known as the "Richards Box" or "Fred's Folly", this device enabled accurate manual fitting of a wireframe physical protein model to electron density maps by overlaying the two in a half-silvered mirror. With the convention, at the time, of building physical models at about one centimeter per &Aring;ngstrom, the device was taller than a person and filled the better part of a good sized room. It was widely adopted by crystallographers worldwide for the next decade, and the first computer-based replacements were initially called "electronic Richards boxes".
 * Leading an early steering committee for the PDB, and a committee in the early 1980's that persuaded journal editors to require deposition of data in the PDB for structures reported in their journals, and the NIH to require data deposition as a condition for continued funding of research. These policies were established at a crucial time, just before a rapid increase in the rate at which macromolecular structural solutions were reported.

Despite Richards' advocacy for the Protein Data Bank, it appears that his first crystal structure was never deposited in the PDB, since the earliest Richards structures there for RNAse S are from the early 1990's.